Diminished Hematopoietic Activity Associated with Alterations in Innate and Adaptive Immunity in a Mouse Model of Human Monocytic Ehrlichiosis
Diminished Hematopoietic Activity Associated with Alterations in Innate and Adaptive Immunity in a Mouse Model of Human Monocytic Ehrlichiosis
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DOI：
10.1128/iai.01550-08
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发表时间：
2009-09-01
影响因子：
3.1
通讯作者：
Winslow, Gary M.
中科院分区：
文献类型：
--
作者：
MacNamara, Katherine C.;Racine, Rachael;Winslow, Gary M.
人单核细胞埃立克体病（HME）是由查菲埃立克体引起的蜱传疾病。患者表现出诊断上重要的血液学变化，包括贫血和血小板减少，尽管异常的基础尚不清楚。为了开始理解这些变化，我们使用了埃立克体病小鼠模型来确定所观察到的感染诱导的血液学变化是否与造血活动的改变有关。小鼠埃立克体（Ehrlichia muris）是与小鼠埃立克体（E. chaffeensis引起贫血、血小板减少和骨髓细胞结构的显著减少。感染后第10天和第15天进行的CFU检测显示多能骨髓和红系祖细胞显著减少。这些变化伴随着骨髓中未成熟粒细胞频率的增加和B淋巴细胞频率的减少。在脾细胞结构和结构中观察到同样显著的变化，感染小鼠表现出广泛的髓外造血。脾肿大是E.小鼠感染，与扩大和紊乱的边缘区和近66倍的Ter119（+）红细胞水平的增加有关，表明脾红细胞生成。我们推测埃立克体感染相关的炎症抑制骨髓功能，诱导B细胞迁移，并在脾脏中建立造血活性。我们认为，这些变化，这可能是必不可少的提供先天性和获得性免疫细胞，以对抗感染，也是部分负责血细胞减少症和其他临床特征的HME。
Human monocytic ehrlichiosis (HME) is a tick-borne disease caused by Ehrlichia chaffeensis. Patients exhibit diagnostically important hematological changes, including anemia and thrombocytopenia, although the basis of the abnormalities is unknown. To begin to understand these changes, we used a mouse model of ehrlichiosis to determine whether the observed hematological changes induced by infection are associated with altered hematopoietic activity. Infection with Ehrlichia muris, a pathogen closely related to E. chaffeensis, resulted in anemia, thrombocytopenia, and a marked reduction in bone marrow cellularity. CFU assays, conducted on days 10 and 15 postinfection, revealed a striking decrease in multipotential myeloid and erythroid progenitors. These changes were accompanied by an increase in the frequency of immature granulocytes in the bone marrow and a decrease in the frequency of B lymphocytes. Equally striking changes were observed in spleen cellularity and architecture, and infected mice exhibited extensive extramedullary hematopoiesis. Splenomegaly, a characteristic feature of E. muris infection, was associated with an expanded and disorganized marginal zone and a nearly 66-fold increase in the level of Ter119(+) erythroid cells, indicative of splenic erythropoiesis. We hypothesize that inflammation associated with ehrlichia infection suppresses bone marrow function, induces the emigration of B cells, and establishes hematopoietic activity in the spleen. We propose that these changes, which may be essential for providing the innate and acquired immune cells to fight infection, are also responsible in part for blood cytopenias and other clinical features of HME.